Fibromyalgia is a debilitating chronic pain disorder that affects 2% of the population. Many drugs used to treat fibromyalgia are highly addictive, have limited clinical efficacy, and do not treat the cognitive symptoms of fibromyalgia. The long-range goal of our neuroimaging research is to better understand the neurochemistry of fibromyalgia and how alterations in neurotransmission and neuroinflammation relate to treatment efficacy and patient outcome. The objective of this application is to ascertain how the dopamine system in fibromyalgia subjects differs from that of a healthy control population. The central hypothesis is that fibromyalgia patients have a higher dopaminergic tone and a less responsive dopaminergic system relative to normal control subjects, and that these abnormalities are related to the high pain sensitivity and cognitive dysfunction in fibromyalgia. The proposed work will utilize PET and [18F]fallypride (FAL) and standard tracer kinetic modeling methods to study the dopamine system in fibromyalgia. Ten healthy control subjects and ten fibromyalgia subjects will undergo two FAL PET scans, one during a resting (baseline) state, and one during a n-back working memory task. Baseline D2 receptor availability and task-induced change in D2 availability (indicative of dopamine release) will be determined for several brain areas, including prefrontal cortex, insula, anterior cingulate, amygdala, hippocampus, thalamus, and striatal subdivisions (limbic, associative, sensorimotor). Subjects will also undergo pressure/pain threshold testing. Specific Aim 1 of this study will determine if fibromyalgia subjects have a higher basal central dopaminergic tone relative to control subjects, and determine if dopaminergic tone is related to pain sensitivity. Specific Aim 2 will determine if dopamine release induced by a working memory task is reduced in fibromyalgia patients relative to controls, and determine if task-induced DA release is related to task performance. The rationale for this study is that the information gained about the dopamine system in fibromyalgia ultimately will result in selectively targeted non-addictive pharmacotherapies that will be efficacious in treating both the pain and cognitive problems inherent to this disorder. PUBLIC HEALTH RELEVANCE: Studying the dopamine system in fibromyalgia is directly relevant to public health, as it will ultimately reduce use of highly addictive drugs for pain management. Understanding the neurochemistry of pain will lead to better strategies for treatment of pain, including the development of sophisticated non-addictive therapies. We also expect that the results of this study will contribute to the development of neuroimaging protocols that will be used to tailor treatment regimens for patients, based on individual neurochemical patterns.